Study classifies 12 TARDBP variants as likely pathogenic in ALS
Original source
Pathogenicity Classification of TARDBP Variants of Uncertain Significance: An Integrative Clinical Characterization and Functional Validation. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human
Related topics
Researchers used laboratory cell experiments to assess 28 TARDBP variants whose clinical significance was uncertain. They found 22 were functionally abnormal, including 12 classified as likely pathogenic under established genetic guidelines. The study also described clinical features in 35 people with ALS carrying 12 TARDBP variants.
Why this matters
The findings may help clinicians and genetic counsellors interpret some TARDBP test results. The study also supports using patient-derived skin fibroblasts to study these variants. Because the work was performed in cells and provides a preliminary basis for research, it does not yet change ALS treatment.
Limitations and context
This was a primary research study based partly on in vitro cell experiments and a clinical summary of 35 people. Only 28 variants were functionally tested, and the authors describe the therapeutic implications as preliminary. The study does not show that any treatment benefits people carrying these variants.